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New Discovery May Reveal a Pathway to Longer Life

A breakthrough in brain research could lead to treatments that extend life by 20 percent

By Gary Drevitch

You may not really want to live forever — if it's so wonderful, why are all those movie vampires so mopey? But how would you feel about a much longer life, especially if it comes with less cognitive decline? A promising new discovery about how we age could lead to discoveries that extend our lives by 20 percent or more.
Researchers at New York City's Albert Einstein College of Medicine have found that the brain region known as the hypothalamus controls aging throughout the body and that switching a pathway within it off or on can extend (or shorten) the life spans of laboratory mice.
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"Scientists have long wondered whether aging occurs independently in the body's various tissues or if it could be actively regulated by an organ," molecular pharmacologist Dongsheng Cai, the study's lead author, said in a statement. "It's clear from our study that many aspects of aging are controlled by the hypothalamus. What's exciting is that it's possible — at least in mice — to alter signaling within the hypothalamus to slow down the aging process and increase longevity."
The team's results, published online Wednesday in the journal Nature, indicate that a specific, age-related signaling pathway through the body could slow aging and become the key to developing new treatments that combat endemic diseases, like Alzheimer's.
The hypothalamus is tiny, Cai said, "but it is a very crucial structure in the brain in terms of regulation of life-supporting activities," like metabolism, reproduction and growth. He believes inflammation in the hypothalamus has a major effect on how we grow older.

"As people age you can detect inflammatory changes in various tissues," Cai said. "Inflammation is also involved in various age-related diseases, such as metabolic syndrome, cardiovascular disease, neurological disease and many types of cancer."

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Cai's team had previously studied the link between inflammation in the hypothalamus and metabolic syndrome, a combination of health problems that can put you at higher risk for diabetes or heart disease. This time they focused on a specific protein complex they had identified as central to that inflammation. They discovered it was virtually inactive in young mice, but became much more active in the hypothalamus as mice grew older.
In the study, the researchers showed that stimulating the protein accelerated aging, causing earlier death. "The mice showed a decrease in muscle strength and size, in skin thickness and in their ability to learn — all indicators of aging," Cai said. "Activating this pathway promoted systemic aging that shortened the lifespan."

It also shut down the mice's reproductive systems, a further indication that the buildup of inflammation in the hypothalamus triggers the aging process. 
Crucially, the team also demonstrated that blocking the protein's activity slowed aging and increased life spans by about 20 percent. "What's exciting," Cai said, "is that it's possible — at least in mice — to alter signaling within the hypothalamus to slow down the aging process and increase longevity."
The team was able to treat the hypothalamus with a hormone that protected mice from what is typically an age-related decline in the ability to create neurons in the brain. As a result, it appeared they were able to slow age-related cognitive decline, raising the hope that such a strategy could treat similar conditions in humans. "If we inhibit this pathway, we can slow down aging," Cai told Business Insider. "So, that's pretty remarkable."


The new findings focused on one pathway, but as Cai told Business Insider, "there could be other molecules involved altogether. So we can speculate that if we manipulate more than just this pathway, there could be an even greater effect."

Experts commenting on the discovery called it a major breakthrough. Other researchers are now expected to follow Cai's lead in pursuing treatments that exploit the hypothalamus' role in aging.

"This earns a spot in the top 10 or 15 leads that should earn a lot of attention," University of Michigan gerontologist Richard Miller, who did not participate in the research, told The Scientist. In the study, "many different aspects of aging are being slowed together," he noted. "That means that whatever they're working on is somehow slowing that basic aging process itself."
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"I think it’s pretty exciting," said Brian Kennedy, chief executive of the Buck Institute for Research on Aging in California, who was not involved in the study. "In terms of humans, it suggests a new way that you could think of modulating aging pathways," he told The Scientist.
Cai emphasized that while the new findings raise hopes, "It will take some time to develop practical approaches for human beings."

Gary Drevitch was senior Web editor for Next Avenue's Caregiving and Health channels. Read More
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